Compact, integrated system for processing test samples

ABSTRACT

An integrated instrument processes fluid test samples using disposable test devices. The test devices are carried in a carrier. The instrument includes a vacuum station receiving the carrier for batch loading of the test devices with fluid samples to be tested. The user removes the carrier from the vacuum station and inserts it into a loading station of a separate carrier and test device processing subsystem. This subsystem includes a transport system moving the carrier through the instrument where various modules perform operations on the test devices, including sealing the test devices, loading the test devices into an incubation station, incubation of the test devices, test device reading, and test device disposal.

CROSS-REFERENCE TO RELATED APPLICATION

This is a divisional of U.S. patent application Ser. No. 10/695,030filed Oct. 28, 2003, pending.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to test devices and related instruments andsystems that test biological, microbiological, chemical or other typesof samples.

2. Description of Related Art

Biological and other types of samples can be reacted and subjected tochemical or optical analysis using various techniques, includingtransmittance and/or fluorescence optical analysis. The purpose of theanalysis may be to identify an unknown biological agent or target in thesample, to determine the concentration of a substance in the sample, ordetermine whether the biological agent is susceptible to certainantibiotics, as well as the concentration of antibiotics that would beeffective in treating an infection caused by the agent.

In the mid-to late 1970's, engineers and scientists working with theapplicants' assignee and its predecessor in interest developed atechnique for conducting optical analysis of biological samples using asealed test sample card containing a plurality of small sample wells.The technique, and related instruments and devices, came to be known inthe industry as the “Vitek® System”. The Vitek® System was (andcontinues to be) a commercial success.

The cards used in the Vitek System are known in the patent literature,see e.g., U.S. Pat. Nos. 4,118,280, 3,963,355, 4,018,65; 4,116,775 and4,038,151. More recent versions of the cards are described in U.S. Pat.Nos. Des. 382,647, Des. 414,272, 5,609,828, 5,746,980, 5,766,553,5,843,380, 5,869,005, 5,916,812, 5,932,177, 5,951,952, and 6,045,758.

Cards were developed for both identification of unknown microorganismsthat may be present in a sample and susceptibility of a known organismto precisely calibrated concentrations of antibiotics. Duringmanufacture of the cards, the wells are filled with either various typesof growth media for various biological agents, or else concentrations ofdifferent antibiotics, and covered with a transparent sealing tape.

The cards have an external transfer tube port as a mechanism forallowing a fluid sample to enter the card. The cards further include aninternal fluid passageway structure for allowing fluid to enter thewells of the card from the transfer tube port. One end of straw-liketransfer tube is inserted into the transfer tube port. The other end isinserted into an open receptacle (e.g., test tube) containing the fluidsample to be tested. In accordance with the teaching of the prior artCharles et al. U.S. Pat. No. 4,188,280, the card with attached transfertube and test tube are placed into a stand-alone vacuum and fillingsealing machine, known as the Vitek® Filler Sealer. The filling andsealing machine generates a vacuum. When the vacuum is released, thefluid sample is drawn from the test tube into the transfer tube andthrough the internal channels of the card and into all of the samplewells. In the instrument of the prior art Charles et al. '280 patent,after the wells of the card are loaded with the sample, the cards aremanually inserted into a slot in a sealer module in the machine, wherethe transfer tube is cut and melted, sealing the interior of the card.

The cards are then manually removed from the filler/sealer module andloaded into a reading and incubating machine, known as the VITEK®Reader, also described in the Charles et al. '280 patent. The readingand incubating machine incubates the cards at a desired temperature. Anoptical reader is provided for conducting transmittance testing of thewells of the card. Basically, the cards are stacked in columns in thereading machine, and an optical system moves up and down the column ofcards, pulling the cards into the transmittance optics one at a time,reading the cards, and placing the cards back in the column of cards.

The arrangement of the early Vitek System (as described in the Charleset al. '280 patent) has several limitations, in that two machines, afiller/sealer and a reader, are required to process and analyze thecards. Furthermore, additional time and labor are required to conductthe complete analysis of the card. The applicants' assignee laterdeveloped and commercialized a fully automated instrument, referred toherein and known in the art as the “Vitek 2” instrument. The Vitek 2instrument automates both the vacuum loading and sealing operations andcombined them with incubation and reading in a single instrument. Theoverall instrument is described in several patents, including U.S. Pat.Nos. 5,762,873 and 6,086,824, the contents of which are incorporated byreference herein.

Briefly, the “Vitek 2” system provides an automated sample testingmachine that performs dilutions for susceptibility testing, fills thecards with the samples at a vacuum station, and seals the card bycutting the transfer tube, and conducts incubation and opticaltransmittance and fluorescence analysis of the cards, all automatically.The machine provides for novel pipetting and diluting stations,permitting fluids to be added to the test tubes or transferred from onetest tube to another. The machine is capable of conducting simultaneoussusceptibility and identification testing of a sample placed in a singletest tube. The machine provides for rapid, automatic identification andsusceptibility testing of the sample.

The instrument uses a sample tray or “boat” and a test samplepositioning or transportation system that moves the “boat” in fourseparate paths around a rectangular base pan among the various stations.The user places a cassette loaded with cards and test tubes containingsamples into the boat at a loading station. The design of thepositioning system is such that it permits essentially a customconfiguration of stations above the base pan. Expansion of the machineto include additional carousels and reading stations, or addition typesin intermediate procession stations such as dilution stations or vacuumstations, can be readily accomplished.

The test sample positioning system of the Vitek 2 instrument isdescribed in U.S. Pat. Nos. 5,736,102, 5,762,874, 5,798,182, 5,798,084,5,853,667, and 5,897,835. The optical reading station is described inU.S. Pat. Nos. 5,798,085, 5,853,666, and 5,888,455. The incubationstation is described in U.S. Pat. Nos. 5,925,884 and 6,156,565. Thevacuum loading station is described in U.S. Pat. No. 5,965,090. Thecutting and sealing station is described in U.S. Pat. No. 5,891,396. Theentire content of all of the above-listed patents is incorporated byreference herein.

As was the case with the original Vitek System, the Vitek 2 system alsohas been a commercial success. The Vitek 2 system is particularlypopular with larger clinics or testing laboratories that have aparticular need for a high capacity and high throughput testing system.However, there are smaller labs and clinics that need that functionalityand features of a state of the art diagnostic and sample-testinginstrument, but do not necessarily require the high capacity and totalautomation as provided by the Vitek 2 system. There is a need in the artfor a state of the art sample processing instrument, like the Vitek 2,but which is more compact, less-costly and less complex, and more suitedto small and medium scale sample testing enterprises. The presentinvention provides an instrument and methods of operation that meetsthat need.

While this background discussion has set forth the context of theinvention in relation to the closest known prior art, the variousaspects and features of the inventive system are applicable to othertypes of sample testing and processing systems that are known in the artnow or may later be developed. Thus, the inventors do not limit thescope of the invention to any particular sample testing device format,instrument or testing protocol. Moreover, the features of the presentinventive system are applicable to other types of testing and otherinstrument architectures besides biological sample testing and theparticular instrument described in this specification. All questionsconcerning the scope of the invention are to be answered by reference tothe appended claims.

SUMMARY OF THE INVENTION

In a first aspect, an integrated system for processing a plurality oftest samples and test sample devices for receiving the test samples isdescribed. The test samples are received in individual fluidreceptacles. The instrument includes a carrier for carrying a pluralityof the individual fluid receptacles and a plurality of the test sampledevices. Each of the test sample devices are placed in fluidcommunication with a test sample stored in one of the individual fluidreceptacles. The instrument further includes a vacuum station having adoor so as to be adapted for manual insertion of the carrier into thevacuum station and manual removal of the carrier from the vacuumstation. The vacuum station further includes a source of vacuum. Thevacuum source is controlled so as to load the test samples from theindividual fluid receptacles into the respective test sample devices.

The instrument further comprises a set of processing modules forming acarrier and test device processing subsystem. These modules are locatedremote from the vacuum station, i.e., the user must manually remove thecarrier from the vacuum station and then manually load the carrier intothe carrier and test device processing subsystem after completion ofvacuum loading of the test samples. These modules include a module forconducting optical measurements of the test sample devices. The carrierand test device processing subsystem and the vacuum station areintegrated into a single instrument.

In a second aspect, an integrated system for processing a plurality oftest samples and test sample devices is provided. The system uses acarrier holding a plurality of the fluid receptacles and a plurality ofthe test sample devices in a spaced relationship, each of the testsample devices having a transfer tube providing fluid communicationbetween the test sample device and one of the fluid receptacles receivedin the carrier. The system comprises a vacuum station adapted for manualinsertion of the carrier into the vacuum station and removal of thecarrier from the vacuum station. A first door provides the user withaccess to the vacuum station. The instrument further includes a carrierand test device processing subsystem remote from the vacuum station. Thecarrier and test device processing subsystem includes modules orapparatus for sealing the test devices by cutting and sealing thetransfer tubes, incubating the test devices, and reading the testdevices. A second door is provided to give access whereby the user canmanually insert the carrier to the carrier and test device processingsubsystem.

In another aspect, a method is provided for processing a plurality oftest samples contained in open receptacles with test sample devices. Thereceptacles and test sample devices are carried by a carrier. Each ofthe test sample devices have a transfer tube providing fluidcommunication between the test sample device and one of the fluidreceptacles received in the carrier. The method comprises the steps of:

manually placing the carrier into a vacuum station having a chamber andapplying vacuum to the vacuum station chamber to thereby transfer thetest samples into the test sample devices as a batch;

manually removing the carrier from said vacuum station chamber after thetransfer has been completed;

manually placing the carrier into an automated carrier and test deviceprocessing subsystem remote from the vacuum station, and

automatically moving the carrier with a transport system in the carrierand test device processing subsystem to modules automatically sealingthe test sample devices and loading the test samples into an incubationstation. The test devices are subsequently incubated and periodicallyread by a reading station. The vacuum station and the carrier and testdevice processing subsystem are integrated into a single test sampleprocessing instrument.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a preferred embodiment of a compact,integrated system for processing test samples and test sample devices.The instrument includes a vacuum station on the left for vacuum loadingof test sample devices that are received in a carrier, and a separateCarrier and Test Sample Device Processing Subsystem on the right whichprocesses the carrier and test sample devices after the test sampledevices are loaded by the vacuum station.

FIG. 2 is a front elevational view of the instrument of FIG. 1.

FIG. 3 is a top view of the instrument of FIG. 1.

FIG. 3A is a front view of the instrument of FIG. 1 with the front doorsand panels open and the top panel and user access top removed.

FIG. 3B is a detailed front view of the vacuum chamber with the dooropen showing placement of a loaded carrier with test sample devices andtest tubes positioned within the vacuum chamber.

FIGS. 4 and 5 are diagrams of top and front views, respectively, of theinstrument of FIG. 1, showing the general location of specificsub-assemblies and sub-systems in the instrument; familiarity with thesefigures will be helpful in understanding the more detailed drawings inthe subsequent figures, particularly FIGS. 16-21.

FIG. 6 is an elevational view of a test sample device in the form of amulti-well test sample card. The instrument of FIGS. 1-5 is designed toprocess a batch of cards of FIG. 6 at a time by means of a carrier. Thecarrier receives a plurality of the test sample cards of FIG. 6 and aplurality of open receptacles, e.g., test tubes, containing a fluidsample to be tested.

FIG. 7 is a perspective view of a carrier loaded with test sampledevices and open receptacles. When the test sample devices andreceptacles are placed in the carrier, each of the test sample devicesis placed in fluid communication with a sample in an open receptacle bymeans of a transfer tube, as shown.

FIG. 8 is a perspective view of an empty carrier of FIG. 7.

FIG. 9 is another perspective view of an empty carrier of FIG. 7.

FIG. 10 is a top plan view of the carrier of FIG. 7.

FIG. 11 is a side elevational view of the carrier of FIG. 7.

FIG. 12 is a side elevational view of the carrier of FIG. 7, opposite tothat shown in FIG. 11.

FIG. 13 is an end view of the carrier of FIG. 7, showing the handle.

FIG. 14 is an opposite end view of the carrier of FIG. 7.

FIG. 15 is a bottom plan view of the carrier of FIG. 7.

FIG. 16 is a front perspective view of the instrument of FIG. 1, withthe waste collection and carrier loading/unloading doors removed, andwith the front user access door removed.

FIG. 17 is a perspective view of the instrument of FIGS. 1 and 16 withall of the instrument panels and doors removed, showing generally thefront and left hand sides of the instrument, to better illustrate thesubsystems and subcomponents of the instrument, in particular thevacuum, waste disposal, and test sample device reader subsystems.

FIG. 18 is another perspective view of the instrument of FIGS. 1 and 16with all of the instrument panels and doors removed, showing generallythe front and right hand side of the instrument, in order to betterillustrate the subsystems and subcomponents of the instrument, inparticular the waste disposal, sealer, and incubation stationsubsystems.

FIG. 19 is a top plan view of the instrument of FIGS. 16 and 17.

FIG. 20 is a front elevational view of the instrument of FIGS. 16-19.

FIG. 21 is a perspective view of the top of the instrument with the toppanel removed, in order to better illustrate the various components andsubsystems of the instrument.

FIG. 22 is a perspective, exploded view of the sealer station of FIG.20.

FIG. 23 is another perspective, exploded view of the sealer station ofFIG. 22.

FIG. 24 is an assembled, perspective view of the sealer assembly.

FIG. 25 is a side view of the card autoloader subassembly.

FIG. 26 is a perspective view of the card autoloader subassembly of FIG.25.

FIGS. 27 and 28 are two perspective views showing the operation of thecard autoloader subassembly of FIGS. 25 and 26 loading cards into theincubation station of the instrument of FIG. 1.

FIG. 29 is a perspective, exploded view of the transport assembly thatmoves the carrier of FIGS. 7-17 through the various modules or stationsof the Carrier and Test Sample Device Processing Subsystem in theinstrument of FIG. 1.

FIG. 30 is a top plan view of the transport assembly of FIG. 29.

FIG. 31 is an end view of the transport assembly of FIGS. 29 and 30.

FIG. 32 is a detailed perspective view of the carrier-engaging block ofFIG. 29-31.

FIG. 33 is a view showing the movement of a loaded carrier past adetection station detecting the position of the carrier relative to aspecific processing module in the instrument, here the card autoloadersubassembly of FIGS. 25 and 26.

FIG. 34 is a detailed flow chart showing the workflow and sequence ofsteps in the use of the instrument and associated carrier, test samplereceptacles and test sample devices.

FIG. 35 shows the incubation station with the front cover panel removedto better illustrate the carousel.

FIG. 36 shows the incubation station with the carousel removed to show aslot in the air table that provides access for a thermometer to measuredirectly the air temperature in the incubation station.

FIG. 37 shows a portion of the front cover of the incubation stationwith a receptacle for receiving a thermometer.

FIG. 38 is a side view of the portion of the incubation station of FIG.27 showing the receptacle holding the thermometer.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENT

System Overview

An overview of a presently preferred embodiment of a compact, highthroughput instrument for processing test samples will now be describedin conjunction with FIGS. 1-5. The details on the construction andoperation of the instrument will be described later in conjunction withFIGS. 6-34.

The instrument 10 processes a batch of test sample devices in the formof multi-well test sample cards in the illustrated embodiment. Arepresentative test sample card 100 is shown in FIG. 6 and will bedescribed subsequently. The cards 100 are initially loaded in a cassette(carrier) 200 shown in FIGS. 7-15. The carrier 200 further carries a setof fluid receptacles (test tubes) 106 (FIG. 7) that contain a fluidsample. Each test sample device 100 is placed into fluid communicationwith an associated fluid receptacle 106 by means of a transfer tube 102,shown in FIGS. 6 and 7. The sample is loaded into the card by means of avacuum loading station in the instrument 10 in the manner describedbelow.

The instrument 10 of FIGS. 1-5 is a sample processing and datacollection portion of an overall sample testing system. The overallsystem includes a separate stand-alone identification station where barcodes on the test sample devices are scanned, the cards are loaded intothe carrier 200, and the carrier is applied with a bar code and scanned.These functions are similar to the separate identification systemdescribed in the patent of Fanning et al., U.S. Pat. No. 5,869,006,incorporated by reference herein. The overall system further includes aworkstation having a computer processing system that receives data fromthe reading system in the instrument. These identification and computerprocessing aspects of the overall system are not particularly pertinentto the present invention and only insofar as they are relevant will theybe discussed further.

The illustrated instrument was designed as a smaller and lower-costalternative to more complex sample testing instruments, such as thesystem described in the above-referenced Fanning et al. patent, for usein low to medium range applications in both the clinical and industrymarkets. The instrument provides for semi-automated filling, sealing,and loading of the test sample devices, as will be described in detailbelow. However, whereas the prior art Fanning et al. '006 patent and theVitek 2 instrument supported automated diluting and pipetting functions,these functions are performed off-line by the user either manually orusing other equipment. In other words, the user prepares the samples sothat they can be directly loaded into the test sample devices from theirassociated test tube. These off-line tasks will be discussed in moredetail in conjunction with the work flow chart of FIG. 34.

As in the case with the Vitek 2 instrument, the instrument 10 of FIG.1-5 provides a vacuum station 300 for inoculation of the fluid samplesinto the wells 104 of the test sample card 100 FIG. 6. However, in thepresent system the vacuum loading is performed semi-automatically asdescribed herein, not fully automatically. In particular, the usermanually places the loaded carrier into the vacuum station. When thefluid samples enter the wells 104 of the card 100, the fluid samplerehydrates reagents previously loaded into the wells of the card at thetime of manufacture.

After vacuum loading, the carrier 200 is then manually placed into aseparate compartment in the instrument 10 containing a carrier and testsample device processing subsystem 50. This subsystem 50 includes asealing station 400 which operates to seal the cards by cutting thefluid transfer tube 102. The instrument 10 includes a card autoloadersub-system 500 that automatically loads the cards 100 one at a time intoan incubation station 600. The incubation station 600 includes arotating carousel that holds the cards. The cards are held at aprecisely controlled temperature. The incubation system includes a cardeject mechanism that ejects the cards from the carousel one at a timeand places the cards on a transport assembly 700 that carries the cardsto a card reader subsystem 800. The card reader subsystem 800 includestransmittance optics stations that perform periodic colorimetricreadings of the wells 104 of the cards 100. A software algorithmdetermines changes in patterns of individual reagent wells 104 andtranslates those patterns into organism identification or sets ofantimicrobial results. When the reading is deemed complete, the cards100 are sent by the card transport assembly 700 to a card disposalsystem 900, which holds the cards for removal from the instrument by theuser. If further reading is required, the cards are moved back into theincubation station 600 for further incubation and additional reading.

A carrier transport system 1000 is provided in the instrument for movingthe loaded carrier 200 back and forth within the interior of the carrierand test sample device processing subsystem 50 of the instrument 10. Thetransport assembly 1000 is described in conjunction with FIGS. 29-33.

The instrument of FIGS. 1-5 and 16-33 can be scaled up or down to offercapacity for processing 60 test sample cards at the same time, or evenmore. The present discussion will focus on an embodiment forsequentially processing six fully loaded carriers (60 test sampledevices). It will be appreciated that by providing a larger carouselincubation station or a second incubation station and second opticsstation and associated card transport assemblies the capacity coulddouble.

The instrument 10 performs all control of sample well (test sample card)filling and incubation/optical reading. The instrument 10 also supportsa two-step user workflow for test pre-processing: reagent hydration andsample inoculation (vacuum loading). The test pre-processing is followedby the steps performed automatically in the instrument: cassette andtest setup verification using strategically placed bar code reader inthe instrument, card transfer tube sealing, loading of test sample cardsinto the incubation station, reading of the cards, and unloading andreturn to the user of the processed carrier and test tubes. Upon loadingof the cards 100 into the incubation system 600, the instrument controlsincubation temperature, optical reading, and data transfer to theworkstation computer processing system during the test processingperiod. The instrument then ejects the cards upon test finalization, bymeans of transport of the test sample cards into the card disposalsystem 900.

Door and User Interface Features (FIGS. 1-3B)

Referring primarily now to FIGS. 1-3B, the instrument 10 includes a setof panels 12 that cover the internal sample processing apparatus. Theinternal processing apparatus is described in more detail in FIG. 16 etseq. The panels 12 include a hinged vacuum door 302 that provides accessto a vacuum chamber 304, which are part of the vacuum loading system 300in the instrument. The user places a fully or partially loaded cassette200 (a set of up to 10 test sample cards 100, each connected to anassociated test tube 106 via a transfer tube 102, as shown in FIG. 7)into the vacuum chamber 304 in the manner shown in FIG. 3B and closesthe vacuum door 302. A vacuum is drawn in the chamber 304 and therelease of vacuum loads the fluid samples into the wells of the testsample cards 100. As shown in FIG. 4, the vacuum system 300 furtherincludes a vacuum pump assembly 306 that supplies vacuum to the vacuumchamber 304.

The instrument further includes a hinged load/unload door 14. The useropens this door to expose a carrier loading and unloading station 16,best shown in FIG. 3A, and introduces the carrier (loaded) into thecarrier and test sample device processing subsystem 50. The loadedcarrier 200 (with the vacuum loading just complete) is placed inside themachine at the carrier loading station 16 for subsequent processing inthe instrument (sealing, incubation, reading, disposal). The transportsystem 1000 in the instrument engages the loaded carrier 200 andproceeds to move the carrier as a unit to stations in the instrument asdescribed in detail below.

The instrument further includes a waste access door 902 which is part ofthe card disposal system 900. The door 902 is the means by which theuser gains access to a waste compartment 904. A removable receptacle inthe form of a bucket (906, FIG. 16) is placed in the waste compartment904. The test sample cards are dropped into the bucket 906 after thereading process is complete. When the bucket is full, the bucket isremoved, the cards are discarded, and the bucket is replaced into thewaste compartment 904.

The instrument further includes a front user access door 18, a top useraccess door 20, and top service panel side and rear panels, which arenot relevant to the present discussion. These doors provide access forperiodic cleaning of the instrument or service of components in theinstrument. Access to the interior of the instrument 10 is restrictedduring processing for the safety of the user and to ensure uninterruptedprocessing of the cards. The instrument 10 monitors the status of allthe doors via sensors. Doors that provide access to moving parts, suchas the front user access door 18 and load/unload door 14, also have doorlocks that are monitored.

The vacuum door 302 and load/unload door 14 are round recessed doors.The doors pivot in opposite directions to provide an unobstructedtransfer of the cassette 200 from the vacuum chamber 304 to the loadingstation 16. A detent in the hinge for these doors allows the door tostay open greater than 90° until the user is ready to close it. Thehinges are recessed and hidden from view when the doors are closed.

The instrument includes a compact user interface 22. The user interfaceincludes a keypad and LCD screen, which are located on the userinterface front panel, at the top left of the instrument 10 as shown inFIG. 1. The instrument uses the screen to communicate messages about itsoperation and its status. An audible indictor is also used inconjunction with the LCD display to notify the user when a task iscomplete or if an error has occurred. The keypad is used to respond toinstructions, send commands to the instrument, and perform otherfunctions. Indicator lights located next to the Vacuum Door andLoad/Unload Doors provide additional status information to the user.

Test Sample Device 100 Features (FIG. 6)

The illustrated embodiment is designed to process test sample devices inthe form of multi-well test sample cards. Persons skilled in the artwill appreciate that the instrument, and its constituent components, canbe configured to process other types of test sample apparatus, and theinvention is not limited to any particular format or design for testsample apparatus.

A representative test sample card is shown in FIG. 6. The card 100 is aflat, thin object having front and rear surfaces that are covered with aclear, oxygen permeable transparent sealing tape. The card contains 64test sample wells 104 and an internal fluid passage network 108 thatconnects each of the wells to a fluid intake port 110 and fluiddistribution manifold. The fluid transfer tube 102 is automaticallyinserted in the fluid intake port 108 in the manner shown and locked inplace using the teachings of O'Bear et al., U.S. Pat. No. 6,309,890.During vacuum loading of the card, the fluid sample 120 enters the card100 from the fluid transfer tube 102 and travels along the course of theinternal fluid passage network 108. The fluid sample fills the wells 104of the cards, where the fluid rehydrates dried reagents or growth media.Under conditions of incubation, a reaction occurs between the reagentsin the wells of the card and the microorganism in the fluid sample. As aresult of this reaction, the transmittance of light though the wellschanges. The optics in the instrument 10 periodically read the wells ofthe card 100 by obtaining transmittance measurements at particularwavelengths of light.

The cards for use with the illustrated embodiment are described atlength in the patent literature and therefore a more detailed discussionis omitted. The reader is directed to the following U.S. patents forfurther details: U.S. Pat. Nos. 5,609,828; 5,746,980; 5,670,375;5,932,177; 5,916,812; 5,951,952; 6,309,890 and 5,804,437. Each of thesepatents is incorporated by reference herein.

Carrier 200 Features (FIGS. 7-15)

Referring now to FIGS. 7-15, the carrier 200 or cassette is a moldedplastic component that holds a set of test sample cards 100 andassociated test tubes 106. In the illustrated embodiment, the carrier200 holds a maximum of 10 test cards in specially fitted slots 202. Thefront portion 204 of the cassette 200 has a test tube slot 206 for eachtest tube 106. The slots are numbered 1-10 across the front of thecassette for identification purposes. A handle 208 on the right sideallows for one-handed carrying capability. A removable bar code label210 is applied to the opposite side of the carrier 200 in the flat panelportion 215 (See FIGS. 7 and 14). The bar code 210 provides cassetteidentification when read by a bar code reader in the instrument 10. Eachof the test sample cards is applied with a bar code 120, as shown inFIG. 7.

The user loads the carrier 200 with tubes 106 of patient isolates (or,more generally, a fluid sample) and test cards 100 before placing thecarrier in the vacuum chamber 304 (FIG. 3A) for the filling process. Theasymmetrical shape of the carrier 200 and receiving structures in thevacuum chamber 304 as shown in FIG. 3B ensures that the carrier 200 isproperly loaded into the instrument (i.e., the handle 208 is towards thefront of the instrument). Upon completion of the vacuum loading process,the user opens the door 302 to the vacuum chamber 304 and removes thecarrier 200 from the vacuum chamber 304 and places it in the load/unloadstation 16.

The carrier 200 is a main component of the transport system 1000. Aspecial block feature in the transport system 1000 enables the transportsystem to move the carrier through the processing stations in thecarrier and test sample device processing subsystem 50 and back to theload/unloading station 16. Optical interrupt sensors in the transportsystem detect slots 212 (FIGS. 8, 9 and 15) that are formed into thebottom of the carrier 200. The optical interrupt sensors and the slotsallow the instrument microcontroller to track the cassette location. Theinterrupt slots 212 are U-shaped voids formed in a rib 214 formed in thebottom of the carrier 200. Each slot 212 is positioned in registry withthe position of the card directly above it. Therefore, when theinterrupt sensors detect the position of a slot 212, they are alsodetecting the position of the associated card. This feature facilitatesprecise carrier positioning for automated sealing operations andautomatic loading of the cards from the carrier 200 into the entranceslot in the incubation station.

Vacuum Station 300 Features (FIGS. 1-4, 7, 17)

With reference to FIGS. 1-4 and 7, the user places a carrier 200 loadedwith test sample cards 100 and test tubes 106, such as shown in FIG. 7,into the vacuum chamber 304 of FIG. 3A and closes the door 302. Thevacuum process is activated via the user interface 22 keypad. A siliconseal 306 on the vacuum chamber door 302 presses against the front panelsurface 308, sealing the vacuum chamber 304. The vacuum pump in thevacuum pump assembly 306 (FIGS. 4, 17) starts drawing the air from thechamber 304. The air escapes from the card channels and wells via thetransfer tubes and up through the suspension or fluid sample in the testtubes 106. The channels and wells inside of each card are now in avacuum.

The vacuum station fills the card with the inoculation suspension in thetest tubes 106 using vacuum displacement principles taught in Fanning etal., U.S. Pat. No. 5,965,090, the content of which is incorporated byreference herein. The rate of change of the vacuum is monitored andregulated by a pneumatic servo feedback system under microcontrollercontrol.

In particular, after a short period, the vacuum is released at acontrolled rate from the vacuum chamber. The increasing air pressureinside the chamber forces the suspension from each test tube 106 throughthe transfer tube 102 and into the internal fluid channels and wells 104of the card 100. This process of course occurs simultaneously with allthe cards in the carrier in the vacuum chamber. The result is vacuumloading of all cards 100 in the carrier 200. The carrier 200 is nowready for insertion into the loading station 16 of FIG. 3A andprocessing therein by the carrier and test device processing subsystem50 in the remainder of the instrument 10.

Carrier and Test Sample Device Processing Subsystem (FIGS. 1, 4, 5,16-33)

Now that the carrier 200 and test devices 100 have been processed in thevacuum station 300, the carrier 200 is now ready for placement into theloading station 16 and processed by the remainder of the instrument'ssubsystems, collectively referred to herein as the carrier and testsample device processing subsystem 50. This group of components includesthe transport system 1000, sealing station 400, card autoloadersubassembly 500, incubation station 600, card transport subsystem 700,optical reading station 800 and disposal system 900. These features willbe described in further detail in this section.

Carrier Loading and Unloading Station 16 (FIGS. 1, 3A, 16)

The load/unload station 16 is where the operator manually loads thecarrier of filled cards to start the sealing, incubation, and readingprocesses. The load/unload door 14 (FIG. 1) will remain locked at alltimes unless the user is ready to load or unload a carrier. The door 14is shown removed from the instrument in FIG. 16 in order to betterillustrate the loading/unloading station 16.

The loaded carrier 200 (FIGS. 3B, 7) is loaded into the instrument 10through the open load/unload station door 14. A reflective sensor 1040(FIG. 17) in the load area is used to sense the presence of a carrier200 in the load/unload station 16. An indicator light 32 above theload/unload station 16 indicates the status of the load/unload stationto the user. Once the door 14 is closed, the processing cycleautomatically initiates.

The transport system 1000 (FIGS. 29-33) moves the carrier 200 by pullingor pushing it through each processing station within the instrument inthe manner described below. The instrument microcontroller keeps trackof where the carrier 200 is located and the status of the transportsystem utilizing the slots 212 molded into the bottom of the carrier(described above) and optical sensors 1050 A-C (FIG. 29) that arestrategically placed in the transport system 1000. The transport system1000 moves the carrier from the load/unload station 16 to a bar codescanner where the carrier bar code (FIG. 7) and test sample bar codesare read, the sealer station 400, the card autoloader station 500 wherethe cards are loaded into the carousel incubation station 600, and backto the load/unload station 16 for removal of the carrier 200 and thetest tubes plus transfer tube 102 remnants. The carrier is parked at theload/unload station 16, the door 14 unlocked and the operator notifiedby the load/unload indicator light 32. The carrier 200 can then beremoved allowing disposal of the processed test tubes 106 and transfertube 102 waste, making the carrier ready for testing of the next batchof test cards and associated fluid samples.

Bar Code Reader Station 60 (FIGS. 4, 5, 20, 17)

A bar code reader station 60 (FIGS. 4, 5) is positioned in theinstrument 10 generally below the reading station 800. The station 60automatically scans the bar code information on each carrier 200 andtest card within the carrier 200 (see FIG. 7) as they pass through thestation. The bar code reader station 60 consists of a bar code scanner62 (FIG. 20) and a card sensor 1042 (FIG. 17). The card sensor 1042 islocated on the housing of the incubation assembly 600 as close to thecards in the cassette as possible. The card sensor 1042 confirms thepresence of a card 100 in the carrier 200 and the slot location. Theslots 212 in the bottom of the carrier allow the transport system 1000to position each card in front of the bar code scanner 62.

As shown in FIG. 7, each card 100 has a factory applied bar code 120that includes information such as test type, lot number, expiration dateand a unique sequence number. When the card bar codes 120 are scanned atthe separate workstation at the time of loading cards into the carrier200, the instrument's bar code reader 62 provides an additional level ofsecurity by verifying that the cards 100 are loaded as indicated by theuser. If the bar codes are not scanned at the separate workstation(“load and go” mode), the lab technician's worksheet can be used forverifying that cards 100 are loaded in the carrier 200 as indicated.

Successfully scanned carriers 200 and test cards 100 are allowed tocontinue to the sealer station 400. Carriers 200 and cards 100 thatcannot be read at the station 60 due to errors such as missing ordamaged bar codes, expired cards, and unsupported card types, arereturned to the load/unload station 16 and the user notified via theuser interface 22 or indicator light 32. The user is given theopportunity to correct the problem and reload the carrier 200 within alimited amount of time.

Sealer Station 400 (FIGS. 4, 6, 7, and 17-24)

With reference to FIGS. 4, 6, 7, and 17-24, before a test card 100 canbe incubated and read, the wells 104 of the test sample card must besealed off from the outside environment. The sealer station 400 providesthis function for all cards loaded into the carrier 200, one at a time.The sealer station 400 melts and seals the transfer tube 102 using aretractable heated nichrome wire 402, and thereby seals the cards. Thisoperation will now be described in further detail.

After a carrier 200 is loaded into the instrument, a transport block inthe transport system 1000 engages with the carrier 200 and pulls thecassette 200 along the transport system track through a carrier sensor1040, a card sensor 1042, and the bar code scanner 62. If the carrierpasses inspection, it is moved back along the transport system 1000track toward the load/unload door 14 where the sealer station 400operates to cut and seal all the cards in the carrier 200.

In particular, as the carrier 200 moves through the station 400, the hotwire 402 is translated downwardly and at an angle through an aperture404 in an enclosure or housing 406 to the same elevation of the transfertubes 102 in the carrier 200, and thereby exposed to each transfer tube102. As the carrier 200 is slowly advanced by the carrier transportsystem 1000 each transfer tube is forced past the hot wire 402. The hotwire 402 causes the plastic transfer tube 102 to melt, separating themajority of the transfer tube, which falls into the test tube 106. Theremainder of the transfer tube forms a short, sealed stub (e.g., 1.5 mmin length) extending outward from the fluid intake port 110 in the card(FIG. 6). At the completion of the sealing processing, power is cut offto the wire 402 and it is retracted back into it's housing 406 toeliminate user contact. The temperature of the wire 402 is controlled bya microcontroller controlled constant current source, as described inKarl et al., U.S. Pat. No. 5,891,396, which is incorporated by referenceherein.

The overall operation of the sealer to cut the transfer tubes 102 issimilar to the process described in the Karl et al. '396 patent. Ascards 100 move past the sealer, the transfer tubes 102 are forced pastthe hot wire 402 melting the plastic and sealing the cards. The wire 402and its associated assembly 408 then retracts into the housing 406. Thecarrier 200 is then moved to the card autoloader station 500, whichmoves the cards laterally off of the carrier 200 and into the entranceaperture of the incubation system 600.

The sealer assembly 400 is unique in several respects: a) its method ofelectronic control, b) its mechanical alignment, c) a preloading featurewhere each card is biased against fixed structures in the instrumentprior to cutting and sealing the transfer tubes, and d) featurespreventing unauthorized user access.

As for feature a), a microcontroller ensures reliable cutting andsealing by maintaining a constant current in the hot wire 402 whileretracting or extending the wire 400 through the aperture 404 per thecard/cassette cycle requirements.

As for feature b), the sealer housing or enclosure 406 orients a wireassembly 408 and associated drive mechanism 410 at an angle allowingalignment of the wire 402 using only one motor 412 to control thehorizontal and vertical position. The wire alignment is achieved byadjusting the mounting of the housing 406 in the instrument or thealignment of the drive mechanism 410 to the housing, and/or setting thelimit positions of the motor 412 in firmware.

As for feature c) and d), the wire 402 and its associated assembly 408,and the drive mechanism 410 are ordinarily placed within the housing406. A shield 416 covers the entrance aperture 406. When a card is inposition for sealing, the motor 412 is energized and the motor operatesto move the wire assembly 408 down and at an angle through the aperture406. This action causes the shield 416 to move out of the way to aretracted position. A spring-loaded pad 414 in the wire assembly 408 andlocated in front of the wire 402 makes contact with the edge of a card100 and preloads or biases the cards 100 using a coil spring 415 againsta fixed structure or stop in the instrument. The fixed structure is inthe form of a rail 604 extending lengthwise along the face of theincubation station 600 housing 602. Other constructions are of coursepossible. The wire 402 then cuts through the transfer tube to produceuniform stubs lengths as the cards 100 are moved past the stationarysealer wire 402. After the sealing operation is completed, the motor 412is energized to retract the wire assembly 408 into the housing 406. Asit does so, the rotating shield 416 retracts by gravity to a closedposition covering the aperture 404. This covering of the aperture 404prevents the user from gaining access to the retracted hot wire 402.

As the carrier 200 approaches the sealer station, the transport system1000 slows its movement to a slow speed. The motor 412 in the sealerstation 400 energizes to move the wire subassembly 408 through theaperture 404 and expose the wire 402. The pad or “shoe” 414 is mountedapproximately 2.0 mm in front of the sealer wire 402. The shoe is springloaded by a compression spring 415 shown in FIG. 22. The shoe or pad 414mounts with a single shoulder screw 420 and incorporates ananti-rotation feature. As the card 100 approaches the hot wire 402, theshoe 414 makes initial contact with the card, deflecting the spring 415and preloading the card 100 against the rail 604 (FIG. 27) on theincubation assembly panel 602. This insures consistency in transfer tubestub length. Forward motion of the carrier 200 past the hot wire 402cuts the transfer tube 102, melting the plastic transfer tube 102 andsealing each card. After all the cards 100 in the carrier are sealed,the transport system 100 again reverses direction along its track andeach of the cards is placed in registry with the card autoloader system500 for loading into carousel incubation station 600 to incubate.

The sealer wire 402 in the preferred embodiment is a heated 18 GaugeChromel A wire mounted on a sliding block mechanism 422 inside the metalenclosure or housing 406. The housing 406 positions the drive mechanism410 at an angle, and locates the extended sealer wire/preload shoe 414at the correct height, and prevents user access to the sealer wire 402and drive mechanism. The drive mechanism 410 is mounted at an angle tosimplify the horizontal and vertical alignment. A stepper motor 412extends the hot wire mounting-block 426 at a 30° angle from horizontalto simultaneously adjust the horizontal and vertical position. Thisangle can of course vary in different embodiments and could vary forexample between 20 and 70 degrees. The exact alignment of the sealerwire 402 is adjustable by firmware controlling the limits of the motor412 to ensure a uniform stub length between 1.0 and 2.5 mm. When thecutting and sealing operation is finished, the stepper motor 412retracts the hot wire assembly 408 until a flag 424 on the block 426 inthe drive system is sensed by home position sensor 428 (see FIG. 22).The assembly includes a chain 448 that serves to protect a wire 446supplying current to the cutting wire 402.

As the hot wire assembly 408 and mounting-block 426 is retracted, therotating shield 416 drops down by gravity and covers the housing opening404. The shield 416 has a tang 430 and flange 452. The flange 452 ispositioned inside the elongate opening 454 in the housing 406 when theunit is assembled. The flange 452 contacts the shoulder 426 of themounting-block 426 as the block 426 nears the retracted home position.The tang 430 and flange 452 prevents the user from lifting the shield416 and gaining access to the hot wire. When the sealer motor 412 isenergized, it causes the pin 462 to slide through the slot 460 in thedrive mechanism 410 and thereby extends the hot wire mounting-block 422.The protective shield 406 is pushed open by the contact between the faceof the block 422, which causes the shield to rotate upward, exposing thehot wire 402 and preload shoe 414. The microcontroller supplies aconstant current to the wire 402 sufficient to produce the propertemperature for cutting through the transfer tubes as the cards pass by,melting the plastic and leaving a small stub of the tube to seal theinterior of the card from the atmosphere.

Card Autoloader Station 500 (FIGS. 20 and 25-28)

Referring now to FIGS. 20 and 25-28, the instrument 10 further includesa card autoloader station 500 that loads sealed cards 100 into theincubation station 600. After the cards have been sealed, the carrier200 is moved to the autoloader station 500. The slots 212 in the bottomof the carrier 200 (FIG. 8) allow the transport system 1000 to positioneach card directly in front of the incubator 600 entrance slot 610,shown best in FIG. 28. The slot in the carrier is determined and trackedautomatically by the instrument's internal microcontroller.

The autoloader station 500 includes a reciprocating, motor-driven pushermechanism 502, located above the carrier 200. The mechanism 502 pushesthe card 100 laterally off of the carrier 200 into the carousel (notshown) in the incubation station 600. The incubation station 600carousel is a circular carousel oriented on its side (rotating about ahorizontal axis) having 30 or 60 slots. One of the slots is positionedat the 6 o'clock position directly in alignment with the card entranceslot 610. The pusher mechanism 502 returns home and the transport system1000 and carousel index to the next card position. The loading of thenext card in the carrier 200 proceeds in the same fashion. Uponcompletion of loading all the cards, the transport system 1000 returnsthe carrier 200 and test tubes 106 to the load/unload station 14 andnotifies the user via the indicator 32 and user interface 22.

Referring now in particular to FIGS. 25-28, the autoloader includes amotor 504 that drives a block 506 attached to the card pusher mechanism502. The block 506 has internal threads that engage a threaded shaft 510extending laterally across the path of the carrier 200. As the motor 504drives the block 506, the block 506 and attached pusher 502 slides alonga guide 508. The pusher 502 contacts the cards 100 in the carrier andinserts them automatically into the slot 610 in the incubation station600. The tips 512 and 514 of the shaft 510 and guide 508 are received inapertures in a plate 612 mounted to the housing 602 of the incubationstation as shown in FIGS. 27 and 28. A pair of guides 612 guide thecards 100 into the slot 610.

Incubation Station 600 (FIGS. 16-20, 35-38)

The incubation station 600 in the instrument 10 will now be described inconjunction with FIGS. 16-20 and 35-38. The incubation station includesa circular carousel 604 (FIG. 35). The carousel is covered by a set ofremovable access cover 630 forming an incubation enclosure. The carouselis rotated by means of a motor 632, shown in FIG. 18. The structure andoperation of the incubation station 600 and its associated carousel isbasically the same as set forth in the patent literature, see U.S. Pat.Nos. 6,024,921; 6,136,270 and 6,155,565, the contents of which areincorporated by reference herein. See also U.S. Pat. No. 5,762,873.Accordingly, a detailed description of the construction of theincubation station 600 is omitted for the sake of brevity.

Once the test sample cards have been sealed and the cards loaded intothe carousel via the entrance slot 610, they remain in the carousel 604for the duration of the test period (up to 18 hours) or until thepredetermined time allotment is met. The time allotment varies for eachreagent or type of card. The carousel is contained in atemperature-controlled chamber (incubator), enclosed by the access cover630.

The carousel 604 itself in a preferred embodiment is composed of fourquadrants (called quadrocells or quads), as taught in U.S. Pat. No.6,136,270, together capable of holding up to 60 test cards within theincubator. Alternative configurations are possible. Positioning of thecarousel is accomplished by optical sensors located at the top andbottom of the carousel, which read positioning slots on the outside edgeof the carousel. Each carousel quadrant can be removed independently forcleaning. However, all four carousel quads must be in place in order forcards to be processed.

The incubator system regulates the temperature of the cards in thecarousel. The temperature is monitored and controlled through the use ofprecision thermistors monitored by a microcontroller maintaining at anaverage carousel temperature of 35.5±1° C. Access for a separate userinstalled probe thermometer has been provided to the front of theIncubator Cover, as explained below. This allows the user to verify theaccuracy of the incubator temperature using an independent calibratedthermometer. The rotating carousel system delivers test cards to thecard transport system 700, which moves the cards to the reader station800 four times an hour until the test is completed. The reader headoptics scans each card and returns them to the incubator. The carouselincludes a card eject mechanism 640 shown best in FIG. 18 that ejects acard from the 12 o'clock position in the carousel and places it in atest card transport system 700 (FIG. 16) for transfer to the opticsstation 800 and return to the incubation station 600. This is the sameas described in e.g., U.S. Pat. No. 5,762,873.

FIG. 35 is a front perspective view of the carousel 604 and incubationstation 600 of FIG. 1, with several of the cover panels of theincubation station removed in order to better illustrate the carousel604. The cover panels form an enclosure for the carousel 604 and isolatethe carousel 604 from ambient conditions.

The carousel 604 is vertically mounted and rotates about a horizontalaxis. An air duct 622 is provided on the upper portion of the station600 to allow air to circulate from the front portion of the incubationstation (containing the carousel 604) to the rear of the station behindthe bulkhead 652. A small hole is placed in the rear cover panelparallel to and positioned behind the bulkhead 652 to allow a controlledamount of ambient air into the station. The duct 622 includes anaperture in the bulkhead 652 to allow air to flow down the rear side ofthe bulkhead between the bulkhead and the rear cover panel, where it isblown over a heater which heats the air, and blown by a second fan intoan air distribution table 624 positioned behind the carousel 604, in themanner shown in FIG. 36.

The carousel 604 has a plurality of slots 614 for receiving the testsample cards. The carousel has a substantially open front side portion623 through which the cards are introduced into the slots 614 at thelowermost portion of the carousel at the carousel loading station, andan opposite rear side portion facing the air table 624 and the bulkhead652.

FIG. 36 is a perspective view of the incubation station of FIG. 35 withthe carousel 604 removed, in order to better illustrate the air table624 and air distribution cover plate 625 features of the incubationstation. The air table 624 receives warm air from a heater and fanassembly behind the bulkhead 652. The air table 624 has an airdistribution cover plate 625 that encloses the air table 624 which ispositioned in registry with the slots 614 of the carousel 604. The coverplate 625 has a plurality of elongate openings 626 formed therein thatdirect the warmed air over the rear side portion of the carousel andover the cards in the carousel slots. In order to promote adequate airflow over the cards, the rear side portion of the carousel adjacent toand opposite the air distribution cover plate 625 is substantially openand free of obstructions so as to permit substantially uninterrupted airflow over the test sample cards.

A notch 670 is formed adjacent to the side of the air table to allowaccess for a thermometer probe to the interior of the air table 624 tothereby allow a user to obtain an instantaneous temperature reading ofthe air in the air table, prior to the air flowing over the test samplecards. As shown in FIG. 37, an insert retainer or receptacle 672 ismounted to the cover panel 602 of the incubation station housing inregistry with the notch 670 to thereby provide a means for holding thethermometer in place. The receptacle 672 includes a tang 674 which gripsthe thermometer 676, as shown in FIG. 38. The face of the thermometer676 includes a display for displaying the temperature. The thermometer676 probe is shown in dashed lines in FIG. 38.

The temperature monitoring system described herein is believed unique inits application to a instruments of this type. The present designsimplifies the integration of a direct readout thermometer 676. Thethermometer is able to measure the incubator air table temperature usingthe retainer 672 to position the thermometer tip at the appropriateangle and location inside the air table 624. The external thermometer676 gives a direct and accurate reading of the internal temperaturewithout disturbing the ongoing test.

Our temperature monitoring system has many unique features, the mostsignificant of which is the location of the external thermometer. Thethermometer probe is positioned in such a way that it monitors the warmair directly before the air hits the cards. This location is significantbecause the air cools slightly as it crosses the cards, and thetemperature to monitor is the air temperature as it begins to hit thecards. Extensive testing was performed to find an accessible locationthat accurately reflects the internal temperature of the incubator. Thepositioning of the thermometer is important and is aided by severalunique features of the system. First, there is the notch 670 molded intothe incubator chassis where the tip of the thermometer probe fits (seeFIG. 36). This notch allows the thermometer to measure the air flowingbehind the air table, which would otherwise be unreachable. The secondunique feature of the thermometer positioning is the thermometerretainer or receptacle 672, as seen in FIG. 38. This mount holds thethermometer 676 at an angle necessary to position the probe in the notch(see FIG. 38). The angled entrance allows the probe to pass over thecarousel without interfering with the carousel motion. It also holds thethermometer at the appropriate distance from the front of the incubatorbulkhead 652 so the tip of the probe does not hit the bulkhead. Themount also has a clip 674 to hold the thermometer in place. Thethermometer is snapped into the receptacle 672 and is not able to slidealong any of the three axes that would affect its visual reading. Thethermometer can rotate in place, though, as this does not affect theaccuracy of the temperature readings.

A convenient point for the user is that the system was designed to use astandard traceable ⅛ in diameter probe thermometer. Should thethermometer break or lose calibration, it can be easily replaced. Thesnap-in receptacle also allows the thermometer to be easily removed forcleaning and calibration. Though this external monitoring system wasdesigned with the industry users in mind, clinical users also appreciatethe ease of manually verifying the temperatures reported by theinstrument firmware. Another benefit is that the temperature reported bythe thermometer is instantaneous. The firmware only reports incubatortemperature as a running three-minute average. Should the instantaneoustemperature be needed, the user can easily measure it manually. Suitablethermometers 676 include Fisher Scientific Traceable Jumbo DisplayDigital Thermometer (part no. 14-648-47) and VWR Scientific ProductsJumbo Display Digital Thermometer (part no. 77776-720).

Card Transport System 700 (FIGS. 16, 17 and 20)

As best shown in FIGS. 16, 17 and 20, the instrument includes a cardtransport system 700 that transfers the cards from the incubationstation 600 past the optical reading station 800 for reading of thewells 104 in the cards 100. The card transport system 700 is essentiallythe same as described in the prior U.S. Pat. Nos. 5,798,085; 5,853,666;and 5,888,455, which are incorporated by reference herein. Accordingly,a more detailed description is omitted for the sake of brevity.Basically, the card is held in a vertical attitude between a belt 704and a ledge 702 and moved from right to left and left to right by meansof a motor driving the belt 704 back and forth. The ledge includes aslot feature for holding cards in the vertical position as the beltdrives the cards back and forth. As the cards are moved past thetransmittance optics heads, the cards are moved in a precise fashion asexplained below to obtain transmittance measurements for each of thewells in the card at a multitude of positions across the width of thewells. The card includes built-in alignment sensor stop holes 130 (FIG.6) to accurately position the wells in the optical system.

Reading Station 800 (FIGS. 4, 5, 16 and 17)

Once the cards are placed in the card transport system 700, they aremoved past the reading station 800. The reading station includes twotransmittance optics modules 802 (see FIGS. 16 and 17) that are orientedvertically, in the same direction as the columns of wells in the card.Each module 802 obtains measurements from one column of wells. Together,the modules 802 obtain transmittance measurements of the wells of thecard in two columns of wells at the sane time. The construction andmanner of operation of the optical reader station 800 is essentially thesame as described in the prior U.S. Pat. Nos. 5,798,085; 5,853,666; and5,888,455, therefore only a general overview and discussion will be setforth herein for sake of brevity. Unlike these patents, the illustratedembodiment provides only transmittance measurements, but of coursefluorescence measurements could be taken as described in these patentsby either replacing one of the modules 802 with a fluorescence module(see U.S. Pat. No. 5,925,884) or adding a fluorescence module to providethree modules. Additional modules of course could be provided.

The card 100 is positioned and read by the transmittance optical systemmodules 802 and returned to the carousel slot from which it was ejected.No data analysis takes place in the instrument; optical data iscollected and transmitted to a remote workstation for analysis. Raw datamay be queued and transmitted to the workstation later, in the eventthat communications between the instrument and workstation is notoccurring.

The reader station 800 scans each of the cards 100 once every fifteenminutes, for four scans per hour. Each time the card is read, it returnsto the carousel to be incubated until the next reading cycle. After thelast reading cycle is complete, the card is transported through theoptics to the card disposal system 900 for card ejection into the wastecollection container.

The reader system 800 and card transport system 700 together performscard positioning and optical data collection in order to periodicallymonitor the growth of organisms inside the wells of the test cards.Optical transmittance data is used to quantify organism growth bymeasuring the optical transmittance of each well versus time. Theillustrated embodiment currently supports two types of optics modules802. The first module 802 has 660 nm LEDs illumination sources for eachwell. The other module 802 has 428 nm and 568 nm LEDs for each well.Development of a third module with additional wavelengths is of coursepossible.

Each optics module 802 has 8 measurement LEDs so that it can read 8sample wells per column. Each card has 8 (or 16) columns of wells for atotal of 64 wells per card. Each module 802 includes not only thetransmittance LED light source for each well but also a detector foreach well that captures the LED light after passing through the well.The detectors use silicon photodiodes. Sampling takes place as the card,with its 8 columns of 8 sample wells, moves through the optical path(from LED to photodiode) of the modules 802. The reading system scansacross each well as the card is moved by the transport system 700 in 16spatially separated steps, taking 3 readings per step. This data is thenprocessed to reduce the effect of any bubbles that may have formed inthe wells. The readings are smoothed and the peak value is chosen.

The emitter and detector housings in the modules 802 are hinged for easeof servicing and access to the optics area for cleaning. This detectionsystem is capable of auto calibrating internally through air for 30% to100% transmission (no light to full light). The optics is calibrated to100% transmission through air automatically before reading each card.

Disposal System 900 (FIGS. 16, 17, 20)

Once incubation and optical testing of a test sample card 100 iscomplete, the card is automatically removed from the carousel in theincubation station 600, passed through the reader station 800, andtransferred to a disposal system 900. The disposal system includes adisposal enclosure 904 that holds a waste container 906, and a ramp 908that directs the card from the edge of the card transport system 700into a chute 910 positioned directly above the waste container 906. Thewaste container is removable from the instrument 10 and is accessed viathe door 902 shown in FIG. 1. The card is transported to the ramp 908simply by operating the belt in the transport system 700 to the left tocarry the card past the edge of the left-hand ledge 702.

The waste collection station 900 is located below the vacuum station 300at the front of the instrument 10. It houses a removable waste container906 (see FIG. 16) and a sensor (not shown) to detect when the containeris installed. The user is notified when the waste container 906 is fullor jammed by means of the user interface 22. Software in the instrumenttracks the number of cards added to the container after it has beenemptied.

Carrier Transport System 1000 (FIGS. 29-33)

The instrument 10 includes a system 1000 for transporting the carrier200 from the loading and unloading station 16 through the carrier andtest device processing subsystem 50. The transport system 1000 is shownisolated in FIGS. 29-33 in order to better illustrate the components ofthe system. Their interrelationship with the various modules in theinstrument 10 will be appreciated from inspection of the remainingfigures, e.g., FIGS. 17, 19 and 20, and from the following discussion.

Basically, the transport system 100 includes the carrier 200 and atransport subassembly 1002 that moves the carrier 200 back and forth.The transport subassembly 1002 includes a cassette-engaging member 1004in the form of a block that that is adapted to engage the carrier in themanner described below. The transport subassembly 1002 is constructedand arranged such that it moves the block 1004 and the carrier 200 backand forth along a single longitudinal axis between the carrier loadingand unloading station 16, the sealing station 400, and the incubationloading station 500.

The transport subassembly 1002 includes a linear actuator motor 1006that rotates a threaded shaft 1010. The threaded shaft 1010 is receivedin a threaded nut 1005 (FIG. 32) that is attached to the block 1004. Acylindrical guide member 1008 extends between a motor/guide rod mount1018 and a front bearing mount 1020. The front bearing mount 1020 isfastened to the base 1016 of the transport subassembly 1002 as shown inFIG. 29. A pair of lift pins 1012 extend upwards from a drive nutengagement slide 1022 through apertures 1024 in the block 1004. The liftpins are biased by springs 1026 to a lower position, such that when theblock 1004 is positioned at the loading/unloading station 14, the loweredge of the lift pins 1012 are in contact with a ramp or cam surface1014 formed in the base 1016. When the block 1004 is moved by the motor1006 towards the rear of the instrument, the lift pins ride up the ramp1014 and thereby extend through the apertures 1024. In this upperposition, the lift pins can then make contact with features on theunderneath side of the carrier 200 and thereby pull the carrier alongthe track 1030 as the motor 1006 moves the block 1004 towards the rearof the instrument to the bar code reading station 60.

In operation, a reflective sensor 1040 positioned on the side of theincubation station housing as shown in FIG. 17 detects the presence of acarrier in the loading and unloading station 16. As the linear actuatormotor 1006 rotates the shaft 1010, the block 1004 is moved from thefront of the instrument 10 and the two lift pins 1012 are lifted toengage the test sample carrier 200. The pins 1012 are lifted by means ofthe cam surface 1014 molded into the base 1016 of the transportsubassembly 1002. The pins 1012 are attached to the drive nut engagementslide 1022, which holds ball bearing wheels (not shown). The ballbearings ride up the cam surface 1014, lifting the pins 1012, when themotor 1006 is indexed to move the block 1004 to the rear of theinstrument. The carrier 200 is then dragged into the instrument past asecond reflective sensor 1042 (also shown in FIG. 17), which counts thenumber of test sample cards and determines their location in thecarrier. The carrier 200 and its test sample cards are then presented tothe bar code reader station 60, which reads the bar codes on the testsample cards 100 and the carrier 200.

After the bar codes are read, the motor reverses and moves the carriertoward the front of the instrument towards the loading and unloadingstation 14. During the forward travel the hot wire in the sealingstation 400 is deployed and the test sample cards are sealed. The motor1006 reverses again and the carrier 200 is moved to the card autoloaderstation 500 and placed into position where the test sample cards can bepushed off the carrier 200 and into the incubation station 600.

Three optical interrupt sensors 1050A, 1050B and 1050C (FIGS. 29 and 30)track the position of the carrier 200 over the entire travel. The threesensors 1050 are mounted to a single printed circuit board 1052 that issnapped into the transport subassembly base 1016. The carrier 200 slidesover removable and replaceable wear strips 1054. The wear strips 1054minimize friction between the carrier 200 and the base 1016.

As noted above, the linear actuator stepper motor 1006 moves the block1004. The block 1004 restrains the lift pins 1012. The motor's shaft1010 extends nearly the entire length of the subassembly 1002. The endof the shaft 1010 rotates in a pillow block bearing 1020 shown best inFIG. 29. The motor end mounts into an aluminum bracket 1018. The motor1006 is mounted to the bracket 1018 indirectly via four vibrationcontrol grommets and shoulder screws.

The rotating motor 1006 drives an acme threaded nut 1005 (FIG. 32) alongthe length of the shaft 1010. The nut 1005 is pressed into the aluminumblock 1056, which is coupled indirectly to the drive block 1004 via twovibration control grommets 1058 and shoulder screws 1060. The shoulderscrews 1060 allow the nut 1005 to self align, preventing the nut 1005from binding with the shaft 1010. The grommets 1058 prevent noisegenerated by the nut 1005 from transmitting through the drive block 1004and into the base 1016.

The drive block 1004 is moved horizontally by the nut 1005. When movingtoward the front of the instrument, a bearing surface 1060 on the block1004 pushes the rear surface 220 (FIG. 14) of the carrier 200. Whenmoving toward the back of the instrument, the two lift pins 112 liftthrough the holes 1024 in the drive block to engage a rib 222 on theunderside of the sample carrier (see FIG. 15).

When the drive block 1004 is at the front, the block functions as a stopfor a new sample carrier 200 being inserted into the instrument. Whenthe drive block 1004 is at the back of the instrument, a reflectivesensor 1064 (FIG. 29) detects it and indicates to the instrumentmicrocontroller that the block 1004 is in its home position.

Three optical interrupt sensors 1050A, 1050B and 1050C are mounted tothe printed circuit board 1052. The use of the circuit board 1052eliminates the wires screws required when mounting the sensors directlyto the base 1016. The sensors 1050A, 1050B and 1050C detect the notches212 on the underside of the carrier 200, as explained above. Each notchcorresponds to the location of a test sample card. The sensors arelocated on the printed circuit board at the card counter reflectivesensor position (sensor 1050A), the bar code reading position (sensor1050B), and the incubator loading position (sensor 1050C). The sensors1050 A-C allow the carrier's position to be continuously monitored.

The lift pin subassembly consists of two vertical pins 1012 mounted intoan aluminum block 1022 containing two ball bearing rollers (not shown)at the base of the pins, functioning as wheels. The horizontal surface1066 the wheels roll on is stepped near the front of the instrument toprovide the cam or ramp surface 1014. The step is angled to allow thewheels to roll up and down, raising and lowering the pins 1012.Compression springs 1070 on the pins between the drive block 1004 andthe body of the lift pin subassembly ensure that lift pin subassemblydrops when rolling down the cam 1014.

Rails 1072 are provided to constrain the carrier's motion to forward andbackward. The wear strips 1054 are mounted on the left and righthorizontal surfaces of the base 1016 as shown in FIG. 29 to provide alow friction and wear surface for the carrier 200 to slide on.

The front cover 602 of instrument incubator station 600 provides threefunctions for the transport system. Firstly, a horizontal rib 1080 (FIG.17) prevents test sample cards from sliding off the right side of thecarrier 200 prior to insertion into the incubation station 600.Secondly, the reflective sensor 1040 (also FIG. 17) mounted near thefront determines when the carrier 200 is present in the loading station.Thirdly, the sensor 1042 mounted just behind the sensor 1040 counts thetest sample cards 100 and determines their location on the carrier 200.

As best shown in FIGS. 3A and 16, the front panel of the instrument hasa tapered entryway in the loading and unloading station 16 for loadingfor the carrier 200. The carrier 200 is inserted until it contacts thedrive block 1014. The door 14 is closed and the sensor 1040 registersthe carrier's presence. The space between the door 14 and drive block1004 is such that the reflective sensor 1040 will always detect thecarrier 200 if it is present in the loading and unloading station.

Control Electronics and Firmware

The instrument 10 includes control electronics and firmware forcontrolling the operation of the various modules and subsystems of theinstrument. The control electronics is conventional. Such electronicsand firmware can be developed with ordinary effort by persons skilled inthe art from the present disclosure, given the present state of the art.

Work Flow (FIG. 34)

The work flow and processing steps for the instrument 10 will now bedescribed in conjunction with FIG. 34 together with the other Figures.At step 1100, the user prepares the sample inoculum off line, loads thefluid samples into the test tubes, scans the bar codes on the cards 100,and loads the cards 100 and test tubes into the carrier (cassette) 200.The bar code may be scanned off line with a separate bar code scanner.The scanning steps may be performed at a separate identification stationhaving a workstation or computer programmed to receive informationregarding the samples being tested, the scans of the bar codes on thecards being used, and the scan of the carrier bar code.

At step 1102, the user opens the vacuum chamber door 302 and loads theloaded carrier (as in FIG. 7) into the vacuum chamber 304, see FIG. 3A.The user then closes the door 302 to thereby seal the chamber.

At step 1104, the user initiates the vacuum cycle filling the cards viathe user interface 22 keypad.

At step 1106, the vacuum pump is energized and a vacuum is generatedinside the vacuum chamber 304. The vacuum displacement fills the cardsin the carrier in the manner described above.

At step 1108, a test is made to see if the reagent fill was successful.The vacuum slope and time are monitored to insurer reagent fill.

At step 1110, if the reagent fill was not successful, the carrierprocessing is aborted as indicated at step 1112 and the user removes thecarrier 200 the vacuum station 300.

At step 1114, if the reagent fill was successful, the user unloads thecarrier 200 from the vacuum chamber 304.

At step 1116, the user opens the door 14 and manually places the carrierinto the loading and unloading station 16. The detection of the carrieris made by the sensor 1040 (FIG. 17).

At step 1118, the transport system 1000 moves the carrier 200 to the barcode reader station 60. En route, the cards 1000 loaded into the carrierare detected by the card sensor 1042 (FIG. 17).

At step 1120, the bar codes in the carrier and on the cards are read bythe bar code scanner in the reader station 60. The bar codes for thecarrier and the cards are compared to the bar codes scanned off-line (ifsuch scanning was done).

At step 1122, the instrument determines whether the bar code read wassuccessful. If not, the process proceeds to step 1124 where thetransport system 1000 moves the carrier back to the loading/unloadingstation 16 and the door 14 is unlocked. At step 1126, the user correctserrors if possible.

If the bar code read was successful, the process proceeds to step 1128.At this step, the transport system moves the carrier to the sealerstation 400.

At step 1130, the sealer station 400 operates to seal each of the testsample cards in the carrier in the manner described above. The transfertube remnants fall into the test tubes. The remaining stub seals thetest sample cards.

At step 1132, a check is made to determine whether the seal of all thecards was successful. This is done by monitoring the hot sealer wirecurrent, monitoring the sealer motor steps, and monitor the transportmotor steps, and if there are no errors, the sealer worked.

If the sealing step was not successful, the process proceeds to step1142 and the test is aborted and the processing proceeds to step 1138.

If the sealing step was successful, the transport system 1000 moves thecarrier 200 to the card autoloader system 500, as indicated at step1134. The card autoloader is described previously.

At step 1136, the card autoloader station 500 operates to load the cardsone at a time into the carousel in the incubation station 600. Theincubator carousel may rotate or index to any available position toaccommodate the next card.

At step 1138, after step 1136 is completed, the transport system 1000moves the carrier 200 with the test tubes and transfer tube remnants tothe loading and unloading station 16.

At step 1140, the user removes the carrier 200 and disposes of the testtubes and their contents. The carrier is now ready for reuse.

At step 1144, the cards 100 are now housed in the incubation station 600where they are incubated at a constant temperature.

At step 1146, the cards are periodically pushed out of their slot in thecarousel and placed into the card transport system 700, where they areshuttled back and forth to the reading system 800. The reading of allthe wells in the card is designed to occur at every 15 minutes.

At step 1148, the transmittance measurements obtained by the opticsmodules 802 are transmitted to the separate workstation viacommunications ports or interfaces in the instrument 10.

At step 1150, a check is made to determine if the reading of the cardsis complete. This would occur such as by whether a reaction has occurredin one or more of the wells such that the periodic reading of the cardsindicates that identification of the sample or susceptibility of thesample can be determined. If the test is not complete (i.e., morereading needs to occur), the processing proceeds to path 1152 and thecard is sent back to its slot in the carousel for more incubation andadditional reading, and steps 1144, 1146, 1148 and 1150 repeat.

If, at step 1150, the reading is complete, a check is made to see if thewaste container in the disposal station enclosure 904 is full. If so,the user is notified at step 1158. If not, the card transport system 700moves the card all the way to the left past the end of the ledge 702 andthe card falls into the disposal system chute 910 and lands in the wastecontainer in the enclosure 904.

At step 1162, the user periodically empties the waste container.

From the foregoing description, it will be appreciated that we havedescribed a method for processing a plurality of test samples containedin open receptacles 106 with test sample devices 100, the receptaclesand test sample devices carried by a carrier 200; each of the testsample devices 100 having a transfer tube 102 providing fluidcommunication between the test sample device 100 and one of the fluidreceptacles 106 received in the carrier 200, as shown in FIG. 7. Themethod comprises the steps of:

manually placing the carrier 200 into a vacuum station 300 having achamber 304 and applying vacuum to the vacuum station chamber 304 tothereby transfer the test samples into the test sample devices 100 as abatch;

manually removing the carrier 200 from the vacuum station chamber 304after the transfer has been completed;

manually placing the carrier 200 into an automated carrier and testdevice processing subsystem 50 remote from the vacuum station 300, and

automatically moving the carrier with a transport system 1000. Thecarrier is moved in a test device processing subsystem 50 which hasmodules that automatically a) seal the test sample devices (sealerstation 400), b) incubate the test sample devices (incubation station600), and c) read the test sample devices (reading station 800). Asshown in the Figures, the vacuum station 300 and the carrier and testdevice processing subsystem 50 are integrated into a single, unitary,compact test sample processing instrument 10.

Variation from the specifics of the disclosed embodiments are to beexpected depending on the configuration of the test devices and otherfactors. The scope of the invention is to be determined by reference tothe appended claims, in view of the above.

1. An integrated system for processing a plurality of test samples andtest sample devices for receiving said test samples, said test samplesreceived in individual fluid receptacles, said system for use with acarrier holding a plurality of said fluid receptacles and a plurality ofsaid test sample devices in a spaced relationship, each of said testsample devices having a transfer tube providing fluid communicationbetween said test sample device and one of said fluid receptaclesreceived in said carrier, the system comprising: a vacuum stationadapted for manual insertion of said carrier into said vacuum stationand removal of said carrier from said vacuum station, said vacuumstation further comprising a source of vacuum, said vacuum sourcecontrolled so as to load said test samples from said individual fluidreceptacles into respective test sample devices; a first door providingaccess to said vacuum station; a carrier and test device processingsubsystem remote from said vacuum station, said carrier and test deviceprocessing system comprising apparatus for sealing said test devices,incubating said test devices, and reading said test devices; and asecond door providing access for said carrier to said carrier and testdevice processing subsystem.
 2. The system of claim 1, wherein saidcarrier and test device processing subsystem comprises: 1) a carrierloading and unloading station remote from said vacuum station adaptedfor manual insertion of said carrier into said carrier and test deviceprocessing subsystem and for removal of said carrier from said carrierand test device processing subsystem; 2) a transport subassembly fortransporting said carrier from said loading and unloading stationthrough said carrier and test device processing subsystem; 3) a sealingsystem for cutting said transfer tubes and sealing said test sampledevices; 4) an incubation station incubating said test sample devices;5) an autoloading station moving test sample devices from said carrierinto said incubation station; 6) a reading station reading said testsample devices; and 7) a disposal system receiving said test sampledevices after the completion of reading of said test sample devices. 3.The system of claim 2, wherein said transport subassembly comprises acarrier-engaging member adapted to engage said carrier, and wherein saidtransport subassembly is constructed and arranged so as to move saidcarrier back and forth along a single longitudinal axis between saidcarrier loading and unloading station, said sealing station, and saidautoloading station.
 4. The system of claim 1, further comprising athird door for providing access to said disposal system.
 5. The systemof claim 1, further comprising an incubation station having a coverpanel, said cover panel providing access for a thermometer measuring thetemperature of said incubation station, said thermometer providingvisual indication of the instantaneous temperature inside saidincubation station.
 6. The system of claim 5, wherein said incubationstation further comprises a carousel and an air distribution chamberthrough which air is supplied to said carousel, and wherein saidthermometer monitors the temperature of said air distribution chamber.7. The system of claim 1, further comprising a bar code reading stationfor reading bar codes on the carrier and the test sample devices.
 8. Thesystem of claim 1, further comprising a sensor station for determiningthe presence of the carrier and the presence and location of the testsample devices in the carrier.